ABSTRACT
To investigate the hypothesized inhibitory effect of cholecystokinin (CCK) released from the small intestine on food intake and gastric emptying, we infused soybean trypsin inhibitor (STI) into the stomach or duodenum of male rats deprived of food for 17 h. Intraduodenal infusions of STI (100-200 mg) before real or sham feeding, or during sham feeding, had no effect on food intake. Intragastric infusions of STI (100-200 mg) also had no effect on gastric emptying. Identical infusions of STI, however, increased bioassayable plasma CCK six to ninefold. The failure of endogenous, small intestinal CCK released by STI to decrease food intake or to decrease gastric emptying is evidence against the hypothesis that the inhibitions of food intake and of gastric emptying are physiological functions of small intestinal CCK in food-deprived rats. In contrast to the negative results with STI, administration of exogenous CCK-8 (2-4 micrograms/kg ip) significantly inhibited food intake and gastric emptying despite producing smaller increases of plasma CCK than STI produced. The reason for the differential effects of exogenous and endogenous CCK is not clear and requires further investigation.
Subject(s)
Cholecystokinin/physiology , Eating , Gastric Emptying , Trypsin Inhibitors/pharmacology , Animals , Cholecystokinin/antagonists & inhibitors , Eating/drug effects , Gastric Emptying/drug effects , Male , Rats , Rats, Inbred Strains , Reference Values , Sincalide/pharmacologyABSTRACT
The satiety effect of slow intravenous infusions of impure cholecystokinin (CCK) was investigated in 5 rhesus monkeys during sham feeding. CCK suppressed sham feeding. The dose for 50% inhibition of sham feeding was about 10 U/kg-hr; 20 U/kg-hr abolished sham feeding. No dose produced retching, vomiting, diarrhea or other behavioral signs of toxicity. These results demonstrate the potency of CCK for inhibiting feeding in the monkey when gastric, intestinal and postabsorptive mechanisms are not activated by ingested food.
Subject(s)
Cholecystokinin/pharmacology , Eating/drug effects , Animals , Dose-Response Relationship, Drug , Haplorhini , Infusions, Parenteral , Macaca mulatta , Male , Motor Activity/drug effects , Satiety Response/drug effectsSubject(s)
Feeding Behavior , Intubation , Macaca mulatta , Macaca , Stomach , Animals , Conditioning, Operant , Drinking Behavior , Food Deprivation , Haplorhini , Male , Motor Activity , Satiation/physiology , Time FactorsABSTRACT
Five rhesus monkeys were infused intravenously with partially purified cholecystokinin (CCK) Just prior to a test meal of solid food after overnight food deprivation; CCK produced large, rapid, dose related suppressions of feeding. The lowest dose tested (5 Ivy U/kg body wt) produced a significant inhibition of food intake (26% suppression, P less than 0.05). Equivalent infusions of partially purified CCK or the synthetic COOH-terminal octapeptide of CCK (a pure fragment with all the biological activity of the full molecule) produced equivalent suppressions. In a second experiment, gastric preloads of a potent releaser of endogenous CCK, L-phenylalanine (L-Phe), and a weak releaser, D-phenylalanine (D-Phe) were compared for their relative abilities to suppress food intake at a test meal in nine rhesus monkeys after overnight deprivation. L-Phenylalanine produced large, rapid, dose-related suppressions of feeding, but D-Phe did not. The threshold dose of L-Phe was 0.5 g/kg (32% suppression, P less than 0.01). Neither CCK nor L-Phe caused signs of illness in these experiments. The results demonstrate that intravenous exogenous CCK suppresses feeding in rhesus monkeys and suggest that endogenous CCK has the same effect; they are consistent with the hypothesis that CCK is a satiety signal.
Subject(s)
Cholecystokinin/pharmacology , Eating/drug effects , Animals , Depression, Chemical , Dose-Response Relationship, Drug , Haplorhini , Isomerism , Macaca mulatta , Male , Phenylalanine/pharmacologyABSTRACT
In rhesus monkeys with knife cuts which disconnected the ventromedial hypothalamus and produced hypothalamic hyperphagia, we have studied a variety of stimuli known to reduce food intake: weight gain, emotionally arousing stimuli, bitter-tasting food, amphetamine, and pre-prandial intragastric infusion of nutrient. We demonstrate that these animals are similar to animals with ventromedial lesions in passing through a "dynamic" phase of overeating and weight gain and then stabilizing their body weight at a new level by reducing their feeding in a "static" phase. These animals are also more sensitive to the inhibitory effects of noise and bad taste in food. They, however, are less sensitive to the anorexic action of amphetamine. These results suggest that the ventromedial region is not crucial for the inhibitions produced by emotional arousal under our experimental conditions, but plays some role in amphetamine anorexia. Amphetamine is likely to have some specific anorexic action beyond its potential for arousal, since the same animals which are sensitive to the inhibitory effects of arousal are also resistant to amphetamine. Finally these hyperphagic animals do not differ from intact controls in the reduction of food intake produced by preloading with intragastric nutrient. This result is not consistent with the concepts that hypothalamic hyperphagia is caused by a disruption of satiety and that the ventromedial hypothalmic region is a crucial "satiety" centre.
